# ROLE OF T CELLS IN IMMUNITY TO CRYPTOCOCCOSIS

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 1989 · $198,069

## Abstract

Cryptococcoses is an often fatal disease caused by a yeast-like
organism, Cryptococcus neoformans.  Cell-mediated immune (CMI)
mechanisms are essential in host resistance against this organism
as emphasized by the fact that individuals with reduced CD4 cell
function, such as patients with the acquired immunodeficiency
syndrome, (AIDS) are more susceptible to this organism than are
normal individuals.  For a number of years, we have been studying
the anticryptococcal CMI response and its regulation and have found
that the antigen shed by the C. neoformans cells is capable of
inducing suppression of the anticryptococcal CMI response.
Suppression is mediated by a complex circuit of cells and factors,
beginning with first-order suppressor T (Ts1) cells induced by
circulating cryptococcal antigen.  The Ts1 cells, or a soluble
factor therefrom, suppress the afferent limb of the CMI response
and induce second-order suppressor T (Ts2) cells which, in
conjunction with third-order suppressor T (Ts3) cells (induced by
immunization with cryptococcal antigen), suppress the efferent limb
of the CMI response.  These cells and their soluble factors also
reduce the animals' ability to clear the organism from infected
tissues.  Our long-range goals are to acquire a sufficient
understanding of the protective CMI response against C. neoformans,
the regulation of the response, and the antigenic components that
stimulate and elicit the response, so that immunotherapeutic
methods can be developed to effectively treat cryptococcoses in
both normal and immunocomprised patients.  In this application, our
three goals for the next five years are focused on elucidating the
cells, factors, lymphokines, antigenic determinants, and processes
involved in the efferent limb of the anticryptococcal CMI response
and the regulation of that response.  We plan to further develop
in vitro systems for analyzing the mechanisms which include the
production and characterization of:  i) anticryptococcal T cell
clones that transfer delayed-type hypersensitivity (DTH)
specifically for cryptococcal antigen and (ii) Ts2 and Ts3 cell
hybridomas.  We will characterize a recently identified cell that
amplifies the anticryptococcal DTH response (Tamp cell) and define
the Tamp cell's role in CMI resistance against C. neoformans.  We
will establish which component(s) in the cryptococcal antigen
(CneF) elicits a DTH response and which suppresses that response.
Achieving these goals will pave the way for designing
immunotherapeutic protocols as well as provide a well-defined model
which can serve as a basis for studying CMI responses and their
regulation in other infectious diseases.

## Key facts

- **NIH application ID:** 3126368
- **Project number:** 2R01AI015716-10
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **SAM.gov UEI:** GY8NMUZQXVS7
- **Principal Investigator:** JUNEANN W MURPHY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $198,069
- **Award type:** 2
- **Project period:** 1980-04-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3126368

## Citation

> US National Institutes of Health, RePORTER application 3126368, ROLE OF T CELLS IN IMMUNITY TO CRYPTOCOCCOSIS (2R01AI015716-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3126368. Licensed CC0.

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