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Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans.
Tissue Antigens. 2004 Jul; 64(1):25-34.TA

Abstract

Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications.

Authors+Show Affiliations

Clinical Hematology, Santo António General Hospital, Porto, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15191520

Citation

Cruz, E, et al. "Involvement of the Major Histocompatibility Complex Region in the Genetic Regulation of Circulating CD8 T-cell Numbers in Humans." Tissue Antigens, vol. 64, no. 1, 2004, pp. 25-34.
Cruz E, Vieira J, Gonçalves R, et al. Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans. Tissue Antigens. 2004;64(1):25-34.
Cruz, E., Vieira, J., Gonçalves, R., Alves, H., Almeida, S., Rodrigues, P., Lacerda, R., & Porto, G. (2004). Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans. Tissue Antigens, 64(1), 25-34.
Cruz E, et al. Involvement of the Major Histocompatibility Complex Region in the Genetic Regulation of Circulating CD8 T-cell Numbers in Humans. Tissue Antigens. 2004;64(1):25-34. PubMed PMID: 15191520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of the major histocompatibility complex region in the genetic regulation of circulating CD8 T-cell numbers in humans. AU - Cruz,E, AU - Vieira,J, AU - Gonçalves,R, AU - Alves,H, AU - Almeida,S, AU - Rodrigues,P, AU - Lacerda,R, AU - Porto,G, PY - 2004/6/12/pubmed PY - 2004/12/30/medline PY - 2004/6/12/entrez SP - 25 EP - 34 JF - Tissue antigens JO - Tissue Antigens VL - 64 IS - 1 N2 - Variability in T-lymphocyte numbers is partially explained by a genetic regulation. From studies in animal models, it is known that the Major Histocompatibility Complex (MHC) is involved in this regulation. In humans, this has not been shown yet. The objective of the present study was to test the hypothesis that genes in the MHC region influence the regulation of T-lymphocyte numbers. Two approaches were used. Association studies between T-cell counts (CD4(+) and CD8(+)) or total lymphocyte counts and HLA class I alleles (A and B) or mutations in the HFE (C282Y and H63D), the hemochromatosis gene, in an unrelated population (n = 264). A second approach was a sibpair correlation analysis of the same T-cell counts in relation to HLA-HFE haplotypes in subjects belonging to 48 hemochromatosis families (n = 456 sibpairs). In the normal population, results showed a strong statistically significant association of the HLA-A*01 with high numbers of CD8(+) T cells and a less powerful association with the HLA-A*24 with low numbers of CD8(+) T cells. Sibpair correlations revealed the most significant correlation for CD8(+) T-cell numbers for sibpairs with HLA-HFE-identical haplotypes. This was not observed for CD4(+) T cells. These results show that the MHC region is involved in the genetic regulation of CD8(+) T-cell numbers in humans. Identification of genes responsible for this control may have important biological and clinical implications. SN - 0001-2815 UR - https://www.unboundmedicine.com/medline/citation/15191520/Involvement_of_the_major_histocompatibility_complex_region_in_the_genetic_regulation_of_circulating_CD8_T_cell_numbers_in_humans_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0001-2815&date=2004&volume=64&issue=1&spage=25 DB - PRIME DP - Unbound Medicine ER -