Immunogenetics of mycobacterial infections in the North Indian population.

Several lines of evidence highlight the genetic basis of risk to develop mycobacterial diseases. Human leukocyte antigen (HLA)-DR2 alleles (DRB1*1501 and DRB1*1502) have been found to be strongly associated with mycobacterial disease, especially the more severe forms such as lepromatous leprosy and multidrug-resistant pulmonary tuberculosis. In this study, DNA-based high-resolution typing techniques of polymerase chain reaction-sequence-specific oligonucleotide probe were used to determine the distribution of HLA-DR/DQ alleles in patients with leprosy and pulmonary tuberculosis. Analysis of different DR2 subtypes based on valine/glycine dimorphism at codon beta86 in pocket 1 of HLA-DR showed an inverse relationship of DR2 alleles with V/G as the severity of disease increased both in leprosy and in pulmonary tuberculosis.

Differential representations of memory T cell subsets are characteristic of polarized immunity in leprosy and atopic diseases.

We identified functionally polarized subsets of CD4 memory T cells on the basis of the expression of CD11a, CD45RA and CD62L. Within the several phenotypically distinct subsets of CD4 memory cells are two that, upon stimulation, produce primarily IL-4 (MT(2), CD45RA(-)CD62L(+)CD11a(dim)) or primarily IFN-gamma (MT(1), CD45RA(-)CD62L(-)CD11a(bright)). In addition, four other phenotypically distinct subsets of CD4 cells have unique cytokine profiles. To determine the clinical relevance of the representation of these cell types, we analyzed blood from patients with the chronic diseases leprosy and atopy. These diseases are characterized as immunologically polarized, since T cell responses in affected individuals are often strongly biased towards T(h)1 (dominated by IFN-gamma production) or T(h)2 (IL-4 production). We show here that this polarization reflects homeostatic or differentiation mechanisms affecting the representation of the functionally distinct subsets of memory CD4 T cells, MT(1) and MT(2). Significantly, the representation of the MT(1) and MT(2) subsets differs dramatically between subjects with tuberculoid leprosy (a T(h)1 disease), or lepromatous leprosy or atopic disease (T(h)2 diseases). However, there was no difference in the cytokine profiles of these or any of the other finely resolved CD4 subsets, when compared between individuals across all disease states. Thus, it is the representation of these subsets in peripheral blood that is diagnostic of the polarized state of the immune system.