Limited T-cell receptor beta-chain diversity of a T-helper cell type 1-like response to Mycobacterium leprae.
Delayed-type hypersensitivity (DTH) is the standard measure of T-cell responsiveness to infectious organisms. For leprosy, the Mitsuda reaction, a local immune response to cutaneous challenge with Mycobacterium leprae, is considered to represent a measure of DTH against the pathogen. We analyzed the diversity of the T-cell receptor beta-chain repertoire in Mitsuda reactions to determine the breadth of the mycobacterial antigens involved. The polymerase chain reaction was used to compare V beta usage in the Mitsuda reaction T-cell lines established and unstimulated peripheral blood. These molecular analyses revealed a skewed T-cell receptor V beta gene usage in the Mitsuda reaction and in T-cell lines from lesions. To examine the reactivity of T cells from these lesions, T-cell lines were tested against the available native and recombinant antigens of M. leprae. T-cell lines derived from Mitsuda reactions responded more strongly to the 10-kDa M. leprae antigen, a homolog of GroES in Escherichia coli, than to other M. leprae proteins. T-cell lines were also shown to proliferate strongly in response to the 17- and 3-kDa proteins. The pattern of the lymphokine mRNA of these cells was reminiscent of the pattern of murine TH1 cells, positive for interleukin-2 and gamma interferon and weakly positive for interleukin-4. These data indicate that a limited array of T cells, perhaps recognizing stress proteins, secrete a type 1 lymphokine profile in the DTH response to mycobacteria.
Uyemura
K
K
Department of Microbiology and Immunology, UCLA School of Medicine 90024.
Ohmen
J D
JD
Grisso
C L
CL
Sieling
P A
PA
Wyzykowski
R
R
Reisinger
D M
DM
Rea
T H
TH
Modlin
R L
RL
D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006801:Humans; D015441:Leprosy, Tuberculoid / Q000276:immunology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000502:physiology; D008970:Molecular Weight; D009166:Mycobacterium leprae / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000942:Antigens, Bacterial; D008222:Lymphokines; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta