CD40 ligand is not essential for the development of cell-mediated immunity and resistance to Mycobacterium tuberculosis.
It has been proposed that the induction of cellular immunity and resistance to intracellular pathogens is dependent upon CD40 ligand (CD40L). In the present study we show that this proposal is not ubiquitously supported. Mice genetically deficient in CD40L (CD40LKO) were resistant to i.v. infection with Mycobacterium tuberculosis when assessed by survival and bacteriologic burden in the spleen, liver, and lungs. Infected CD40LKO mice developed granulomas that lacked epithelioid cells and were less numerous and markedly smaller than those observed in control mice. Upon stimulation with purified protein derivative of M. tuberculosis, CD4+ T cells from infected CD40LKO mice proliferated and produced high levels of IFN-gamma but not IL-4. Finally, spleen cells from CD40LKO mice stimulated with M. tuberculosis produced IL-12, TNF, and nitric oxide levels comparable to those produced by control cells. In contrast to original proposals, these data clearly show that protective Thl immunity can be achieved against intracellular pathogens (e.g., Mycobacterium) independently of CD40L.
Campos-Neto
A
A
Infectious Disease Research Institute, Seattle, WA 98104, USA. acampos@corixa.com
Ovendale
P
P
Bement
T
T
Koppi
T A
TA
Fanslow
W C
WC
Rossi
M A
MA
Alderson
M R
MR
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D023201:CD40 Ligand; D007111:Immunity, Cellular / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000907:Antibodies, Bacterial; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand; D018664:Interleukin-12